title: QM-FISH analysis of the genes involved in the G1/S checkpoint signaling pathway in triple-negative breast cancer.
abstract: This study was conducted to analyze copy number alterations (CNAs) of the genes involved in the G1/S checkpoint signaling pathway of triple-negative breast cancer (TNBC) and to evaluate their clinical value in the prognosis of TNBC. Quantitative multi-gene fluorescence in situ hybridization was used to study CNAs of the genes involved in the G1/S checkpoint signaling pathway, including cyclin d1 (CCND1), c-Myc, p21, cell-cycle-checkpoint kinase 2 gene, p16, retinoblastoma (Rb1), murine double minute 2 (Mdm2) and p53, in 60 TNBC samples and 60 non-TNBC samples. In comparison with the non-TNBC samples, CNAs of the genes involved in the G1/S checkpoint signaling pathway were more frequently observed in the TNBC samples (p = 0.000). Out of a total of eight genes, six (CCND1, c-Myc, p16, Rb1, Mdm2, and p53) exhibited significantly different CNAs between the TNBC group and the non-TNBC group. Univariate survival analysis revealed that the gene amplification of c-Myc (p = 0.008), Mdm2 (p = 0.020) and the gene deletion of p21 (p = 0.004), p16 (p = 0.015), and Rb1 (p = 0.028) were the independent predictive factor of 5-year OS for patients with TNBC. Cox multivariate analysis revealed that the gene amplification of c-Myc (p = 0.026) and the gene deletion of p21 (p = 0.019) and p16 (p = 0.034) were independent prognostic factors affecting the 5-year OS for TNBC. CNAs of the genes involved in the G1/S checkpoint signaling pathway presented a higher rate of incidence in TNBC than in non-TNBC, which could indicate one of the molecular mechanisms for the specific biological characteristics of TNBC. The genes c-Myc, p21, and p16 were correlated with the prognosis of TNBC and therefore may have potential clinical application values in the prognostic prediction of TNBC.
authors.affiliation: 3rd Department of Breast Cancer, China Tianjin Breast Cancer Prevention, Treatment and Research center, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People's Republic of China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Zhang
authors.forename: Yingbo
authors.initials: Y
authors.lastname: Shao
authors.forename: Guofang
authors.initials: G
authors.lastname: Hou
authors.forename: Jingchao
authors.initials: J
authors.lastname: Bai
authors.forename: Weiping
authors.initials: W
authors.lastname: Yuan
authors.forename: Linping
authors.initials: L
authors.lastname: Hu
authors.forename: Tao
authors.initials: T
authors.lastname: Cheng
authors.forename: Anders
authors.initials: A
authors.lastname: Zetterberg
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
mesh_terms: D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics*; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000235:genetics*; D018628:Gene Dosage; D019942:Genes, p16; D006801:Humans; D007091:Image Processing, Computer-Assisted; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D016016:Proportional Hazards Models; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics*; D064726:Triple Negative Breast Neoplasms / Q000235:genetics* / Q000401:mortality
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc